Low Serum Magnesium Tied to Cardiovascular Mortality, but Mechanisms Murky

Low serum magnesium appears to confer greater risks of coronary heart disease (CHD) mortality and sudden cardiac death in middle-age and elderly people, although the reasons for the relationships remain unclear, an observational study shows.

Carotid intima-media thickness, QT interval, and heart rate were explored as potential mechanisms to explain the findings, but adjusting for those factors did not change the associations, Bruno Stricker, MMed, PhD, of Erasmus Medical Center (Rotterdam, the Netherlands), and colleagues report in the January issue of the Journal of the American Heart Association.

“The results from this and previous studies may provide a rationale to design intervention studies to analyze whether magnesium supplementation could prove to be effective in lowering the burden of CHD mortality and [sudden cardiac death],” they say.

Prior studies looking at similar associations have provided conflicting results, so Stricker and colleagues explored the issue using data on 9,820 participants (mean age 65.1 years; 56.8% women) in the population-based Rotterdam Study. Serum magnesium was measured a single time at baseline.

Through a median follow-up of 8.7 years, 23.5% of the participants died. On multivariate analysis, every 0.1-mmol/L increase in serum magnesium was associated with a lower risk for overall CHD mortality (HR 0.82; 95% CI 0.70-0.96) and nonsudden CHD mortality (HR 0.72; 95% CI 0.58-0.88).

In an analysis that divided participants into quartiles based on serum magnesium levels, low levels (≤ 0.80 mmol/L) were tied to greater risks for CHD mortality (HR 1.36; 95% CI 1.09-1.69) and sudden cardiac death (HR 1.54; 95% CI 1.12-2.11) compared with intermediate levels (0.81 to 0.88 mmol/L). High magnesium levels (≥ 0.89 mmol/L) were associated with a lower risk of nonsudden CHD death (HR 0.69; 95% CI 0.48-0.98).

Looking into potential mechanisms, the researchers found that low magnesium levels were associated with increases in carotid intima-media thickness—an indicator of accelerated subclinical atherosclerosis—and QT interval and a reduction in heart rate. None of those findings, however, explained the observed relationships with mortality.

The inability of accelerated atherosclerosis to explain the link between low serum magnesium and CHD mortality “could be due to the small effect size of serum magnesium on [carotid intima-media thickness],” the authors say. “It is therefore unlikely that this small increase would have a large influence on our outcome. Furthermore, no association was found between serum magnesium and incident MI, which would have been expected if the main effect of serum magnesium is through accelerated atherosclerosis.”

The researchers also hypothesized that QT prolongation could be the mechanism underlying the relationship between low magnesium and sudden cardiac death, but adjustment for QT interval did not modify the relationship.

“An explanation for this limited change in effect estimate may be that a single measurement of QT interval does not fully capture all the electrophysiological changes caused by low serum magnesium,” they say. “Another possibility could be that the effect of serum magnesium on QT interval is too small to have impact on the risk of [sudden cardiac death], as it is currently assumed that a minimal increase of 5 ms is necessary to increase the risk of torsade de pointes.”

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Source: 
Kieboom BCT, Niemeijer MN, Leening MJG, et al. Serum magnesium and the risk of death from coronary heart disease and sudden cardiac death. J Am Heart Assoc. 2016;5:e002707.

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